KEYNOTE-185: A randomized, open-label phase 3 study of pembrolizumab in combination with lenalidomide and low-dose dexamethasone in newly diagnosed and treatment-naive multiple myeloma (MM)

Abstract

Background: Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, leading to antitumor immune response. In the phase 1 KEYNOTE-023 trial of pembrolizumab + lenalidomide and lowdose dexamethasone, the treatment combination had an acceptable safety profile and promising preliminary efficacy in patients with relapsed/refractory MM, supporting further evaluation of pembrolizumab for patients with MM. The randomized, open-label, multicenter, phase 3 KEYNOTE-185 study (NCT02579863 ) was designed to compare the efficacy and safety of lenalidomide and low-dose dexamethasone (standard of care) with or without pembrolizumab in patients with newly diagnosed and treatment-naive MM. Methods: Eligible patients must be aged >= 18 years, have newly diagnosed, treatmentnaive active MM with measurable disease and be ineligible for autologous stem cell transplant. Patients are to be randomized 1:1 to receive lenalidomide 25 mg daily on days 1-21 and low-dose dexamethasone 40 mg daily on days 1, 8, 15, and 22 of repeated 28- day cycles, with or without pembrolizumab 200 mg every 3 weeks. Stratification is to be based on age ( < 75 vs >= 75 years old) and International Staging System stage (ISS I or II vs ISS III). Treatment is to continue until progressive disease or unacceptable toxicity. Response is to be assessed every 28 days by Clinical Adjudication Committee blinded central review and by investigator review based on International Myeloma Working Group (IMWG) response criteria. Adverse events (AEs) are to be assessed throughout treatment and for 30 days thereafter (90 days for events of clinical interest) and graded per NCI CTCAE v4.0. Primary end point is to be progression-free survival as assessed by central review according to IMWG criteria; secondary end points are to include overall survival, overall response rate, and safety and tolerability. Enrollment in KEYNOTE-185 is ongoing; ~640 patients are to be enrolled.